Adolescence is a period of high risk for the onset of Major Depressive Disorder (MDD); indeed, adolescent onset of MDD is associated with longer and more severe depressive episodes that are often refractory to treatment. Thus, it is imperative that we identify factors involved in early-onset MDD and develop more effective approaches to early intervention. In attempting to elucidate factors that contribute to the onset and maintenance of MDD, investigators have focused on negatively biased processing of information. The most consistent cognitive bias in depression involves more negative and less positive interpretations of emotionally ambiguous information. Importantly, investigators have shown not only that these biases in interpretation can be modified, but further, that Interpretatio Bias Training (IBT) improves emotion regulation and reduces depressive symptoms. Despite these findings, however, we know little about the mechanisms that underlie these positive effects of IBT. In an effort to gain a more comprehensive understanding of biased cognitive functioning in MDD, researchers have begun to examine neural aspects of biases in this disorder. In this context, investigators have documented abnormalities in function, connectivity, and/or structure in depressed adults in subgenual and dorsal anterior cingulate (ACC), dorsal prefrontal cortex (PFC), and amygdala, all components of emotion regulatory networks. To date, there is little research examining the neural foundations of cognitive biases in depressed children and adolescents or the effects of modifying these biases in depressed youth. The overarching goals of the proposed project are (1) to assess the cognitive, neural, and clinical effects of training designed to reduce negative interpretation biases in depressed adolescents; and (2) to examine neural and cognitive changes that mediate the positive clinical effects of IBT. Results of this project will increase our understanding of neural processes that underlie interpretation biases in depressed adolescents and contribute to the development of more effective interventions for MDD in adolescence.